Frailty predicts increased risk of reintervention in the 2 years after arteriovenous fistula creation.

INTRODUCTION: Frailty is associated with adverse survival and increased hospital use in patients with end-stage kidney disease (ESKD). Dialysis access failure is an important source of morbidity and mortality for these patients. There is limited evidence about the interactions between frailty and haemodialysis access failure. This population-based cohort study aimed to determine if haemodialysis access reintervention was predicted by frailty. METHODS: Routinely-collected hospital data linked with death records were analyzed for all patients with ESKD who had a new arteriovenous fistula or graft (AVF) created between 2010 and 2012 in New South Wales, Australia. Frailty risk was assigned by the Hospital Frailty Risk Score. Multivariate Cox-proportional hazard ratios (HR), adjusted for patient and procedural variables, quantified if frailty was prognostic for adverse haemodialysis access outcomes in the 2 years after AVF creation. RESULTS: Almost one quarter of the 2302 patients who had a new AVF created during the study period were classified as high frailty risk (554, 24.1%). Compared to low frailty risk patients, patients with high frailty had a significantly greater risk of reintervention for AVF failure in the 2 years after creation (HR 1.68; 95% CI 1.45-1.96), adjusted for age, sex and prior AVFs. Frailer patients were also more likely to have perioperative complications, longer hospital length of stay and readmission to hospital. Frailty was associated with a higher risk of mortality at 2 years after AVF creation (adjusted HR 2.65; 95% CI 1.72-4.10). CONCLUSION: Frailty predicted adverse haemodialysis access outcomes, with frailer patients having higher rates of AVF reinterventions. These results can assist clinicians engaging in shared decision-making discussions about dialysis access risks and help personalize dialysis access decisions.

Mixed Evidence of an Association between Self-Rated Hearing Difficulties and Falls: Prospective Analysis of Two Longitudinal Studies.

INTRODUCTION: This study aimed to assess the extent to which a single item of self-reported hearing difficulties is associated with future risk of falling among community-dwelling older adults. METHODS: We used data from two Australian population-based cohorts: three waves from the PATH Through Life study (PATH; n = 2,048, 51% men, age 66.5 ± 1.5 SD years) and three waves from the Concord Health and Ageing in Men Project (CHAMP; n = 1,448, 100% men with mean age 77.3 ± 5.3 SD years). Hearing difficulties were recorded on a four-point ordinal scale in PATH and on a dichotomous scale in CHAMP. The number of falls in the past 12 months was reported at each wave in both studies. In CHAMP, incident falls were also ascertained by triannual telephone call cycles for up to four years. Multivariable-adjusted random intercept negative binomial regression models were used to estimate the association between self-reported hearing difficulties and number of falls reported at the following wave or 4-monthly follow-ups. RESULTS: In PATH, self-reported hearing difficulties were associated with a higher rate of falls at follow-up (incidence rate ratio = 1.15, 95% CI = 1.03-1.27 per a one-level increase in self-reported hearing difficulties), after adjusting for sociodemographic characteristics, health behaviours, physical functioning, balance, mental health, medical conditions, and medications. There were no significant associations between hearing difficulties and the rate of falls based on either repeated survey or 4-monthly follow-ups in CHAMP. CONCLUSION: Though we find mixed results, findings from PATH data indicate an ordinal measure of self-reported hearing loss may be predictive of falls incidence in young-old adults. However, the null findings in the male-only CHAMP preclude firm conclusions of a link between hearing loss and falls risk.

Associations between dietary intake of total protein and sources of protein (plant vs. animal) and risk of all-cause and cause-specific mortality in older Australian men: The Concord Health and Ageing in Men Project.

BACKGROUND: The association between dietary protein intake and the risk of mortality is still controversial. The present study aimed to examine the associations between dietary total, animal and plant protein intake and all-cause and cause-specific mortality. METHODS: Community-dwelling men aged ≥ 70 years were recruited from local government areas surrounding Concord Hospital in Sydney, New South Wales for the Concord Health and Ageing in Men Project (CHAMP). The research dietitian administered a standardised validated diet history questionnaire to capture baseline dietary intake. In total, 794 men participated in a detailed diet history interview at the third wave. Adequacy of protein intake was assessed by comparing participant intake with the Nutrient Reference Values. Total protein intake was categorised into quintiles. Sources of protein were also captured. Mortality was ascertained through the New South Wales death registry. Cox proportional hazard models were used to assess the association between dietary total, animal and plant protein intake and risk of mortality. RESULTS: The mean age of the CHAMP men was 81 years. In total, 162 men died during a median follow-up of 3.7 years. Of these, 54 (33.3%) and 49 (30.2%) men died due to cancer and cardiovascular disease, respectively. There were U-shaped associations between protein intake and all-cause and cancer mortality. In multiple adjusted analysis, the second (hazard ratio [HR] = 0.38; 95% confidence interval [CI] = 0.18-0.82) and third (HR = 0.36; 95% CI = 0.16-0.82) quintiles of protein intakes were significantly associated with reduced risk of all-cause and only second quintile (HR = 0.47; 95% CI = 0.10-0.93) of protein intake was significantly associated with cancer mortality. Each serve increase in animal protein was significantly associated with 12% (HR = 1.12; 95% CI = 1.00-1.26) and 23% (HR = 1.23; 95% CI = 1.02-1.49) increased risk of all-cause mortality and cancer mortality respectively. Conversely, each serve increase in plant protein intake was significantly associated with 25% (HR = 0.75; 95% CI 0.61-0.92) and 28% (HR = 0.72; 95% CI = 0.53-0.97) reduced risk of all-cause and cancer mortality, respectively. No such associations were observed for cardiovascular disease mortality. CONCLUSIONS: Both second and third quintiles of total protein intake were associated with reduced all-cause and cancer mortality. Plant protein was inversely associated with all-cause and cancer mortality, whereas animal protein intake was positively associated with mortality.

Help, I'm a specialist!-Perspectives of recently qualified geriatricians on the experiences and challenges of working as a consultant geriatrician.

OBJECTIVE: To gain insights into the experience and challenges faced by Australasian geriatricians who have recently made the transition from advanced trainee to consultant. METHODS: An interpretative exploratory qualitative study. Geriatricians with five or less years of experience as consultants were recruited by email. Data were collected through semi-structured interviews, with themes identified through open axial coding. RESULTS: Respondents (n = 20) experienced a transition period in which they adjusted to the roles of final decision-maker and manager. Respondents felt relatively confident with their clinical skills, but under-prepared for non-clinical roles associated with becoming a consultant. Most respondents described challenges with career planning. Support networks were considered critical. CONCLUSIONS: This is the first study in Australasia exploring the transition from trainee to consultant geriatrician. Training programs should endeavour to create "consultant-like roles" during advanced training and address non-clinical competencies. Participants perceived that there should be more emphasis on career planning and mentorship.

Branched Chain Amino Acids, Cardiometabolic Risk Factors and Outcomes in Older Men: The Concord Health and Ageing in Men Project.

Increased blood levels of branched chain amino acids (BCAAs) have been associated with cardiometabolic risk factors. Here, we studied 918 community-dwelling older men to determine the relationship between BCAAs and other amino acids with cardiometabolic risk factors, major cardiovascular endpoints (MACE), and mortality. BCAAs had robust associations with many adverse metabolic risk factors (increased glucose, insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), triglycerides; decreased high-density lipoprotein cholesterol). However, paradoxically, participants with lower levels of BCAAs had greater mortality and MACE possibly because increasing age and frailty, both of which were associated with lower BCAA levels, are powerful risk factors for these outcomes in older people. Overall, amino acids that were lowest in frail subjects (BCAAs, α-aminobutyric acid [AABA], histidine, lysine, methionine, threonine, tyrosine) were inversely associated with mortality and MACE. In conclusion, BCAAs are biomarkers for important outcomes in older people including cardiometabolic risk factors, frailty, and mortality. In old age, frailty becomes a dominant risk factor for MACE and mortality.

Predicting chemotherapy toxicity in older adults: Comparing the predictive value of the CARG Toxicity Score with oncologists' estimates of toxicity based on clinical judgement.

AIM: The Cancer and Aging Research Group's (CARG) Toxicity Score was designed to predict grade ≥3 chemotherapy-related toxicity in adults aged ≥65 yrs. commencing chemotherapy for a solid organ cancer. We aimed to evaluate the CARG Score and compare it to oncologists' estimates for predicting severe chemotherapy toxicity in older adults. METHODS: Patients aged ≥65 yrs. starting chemotherapy for a solid organ cancer had their CARG Score (range 0-23) calculated. Their treating oncologist, blinded to these results, independently estimated each patient's risk of severe chemotherapy toxicity (0-100%). Toxicities were captured prospectively. The predictive value of the CARG Score and oncologists' estimates was estimated using logistic regression and in terms of Area Under the Receiver Operating Characteristic curve (AU-ROC). RESULTS: 126 patients from ten oncologists at two sites participated. The median age was 72 yrs. (range 65-84). The median CARG Score was 7 (range 0-17); the median oncologist estimate of risk was 30% (range 3-80%), and these measures were not correlated (r = -0.01). 64 patients (52%) experienced grade ≥ 3 toxicity. Rates of severe toxicity in low-, intermediate-, and high-risk groups by CARG Score were 58%, 47%, and 58% respectively, and 63%, 44%, and 67% by oncologist estimate. Severe chemotherapy toxicity was not predicted by the CARG Score (OR 1.04, 95%CI 0.92-1.18, p = .54, AU-ROC 0.52), or oncologists' estimates (OR 1.00, 95%CI 0.98-1.02, p = .82, AU-ROC 0.52). CONCLUSION: Neither the CARG Score, nor oncologists' estimates based on clinical judgement, predicted severe chemotherapy-related toxicity in our population of older adults with cancer. Methods to improve risk prediction are needed.

Oncologists' perceptions on the usefulness of geriatric assessment measures and the CARG toxicity score when prescribing chemotherapy for older patients with cancer.

BACKGROUND: The use of geriatric assessment (GA) and the Cancer and Aging Research Group (CARG) Toxicity Score by Australian oncologists is low. We sought oncologists' views about the value of GA and the CARG Score when making decisions about chemotherapy for their older patients. METHODS: Patients aged ≥65 yrs. with a plan to start chemotherapy for a solid organ cancer underwent a GA and had their CARG Score calculated. Results of the GA and CARG Score were provided to treating oncologists who then completed a questionnaire on the value of these measures for each patient. RESULTS: We enrolled 30 patients from eight oncologists. Patients had a median age of 76 years and most (77%) were ECOG performance status 0 or 1. Risk category for severe chemotherapy toxicity by CARG Score was low in 7 patients (23%), intermediate in 18 (60%), and high in 5 (17%). The GA provided oncologists new information for 12 patients (40%), most frequently in the domains of function and nutrition. Knowledge of the GA prompted supportive interventions for 7 patients (23%). Oncologists considered modifications to recommended chemotherapy based on the CARG Score for 2 patients (7%) (one more intensive and one less intensive), and based on GA for no patients. Oncologists judged the GA and CARG Score as useful in 26 (87%) and 25 (83%) patients, respectively. CONCLUSION: Although oncologists valued the GA and CARG Score, they rarely used them to modify chemotherapy. The GA provided new information that prompted supportive interventions in one quarter of patients.

Clinical utilities of quantitative ultrasound in osteoporosis associated with inflammatory rheumatic diseases.

Secondary osteoporosis is an important co-morbidity related to inflammatory rheumatic diseases that is attributed to several factors including inflammatory cytokines, inactivity and glucocorticoid treatment. Quantitative ultrasound (QUS) has been utilized in osteoporosis research due to its detectability of bone density as well as bone quality. The current narrative review is to address the potential utilities of QUS in secondary osteoporosis of inflammatory rheumatic diseases, focusing on the clinical aspects of QUS in these diseases, based on the conformity of QUS with dual emission X-ray absorptiometry (DXA), the relationship with disease characteristics, and its capability of fracture prediction. Although limited data demonstrate that QUS had moderate to strong correlation with DXA, and might be useful as a potential imaging tool to screen for osteoporosis, further research is still required for QUS to be utilized effectively for the best outcome in these patients with rheumatic diseases.

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older. Serum-induced SIRT1 expression was not associated with age or mortality, however participants within the lowest quintile were less likely to be frail (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.69, N = 1,309). Serum-induced SIRT1 expression was associated with some markers of body composition and nutrition (height, weight, body fat and lean % mass, albumin, and cholesterol) but not disease. SIRT1 SNPs rs2273773, rs3740051, and rs3758391 showed no association with age, frailty, or mortality but were associated with weight, height, body fat and lean, and albumin levels. There were some weak associations between SIRT1 SNPs and arthritis, heart attack, deafness, and cognitive impairment. There was no association between SIRT1 SNPs and the serum-induced SIRT1 assay. SIRT1 SNPs and serum-induced SIRT1 expression in older men may be more closely associated with nutrition and body composition than aging and age-related conditions.

Normal Values and Clinical Use of Bedside Sonographic Assessment of Postoperative Gastric Emptying: A Prospective Cohort Study.

BACKGROUND: GI dysfunction is common after abdominal surgery. However, assessment and diagnosis currently lack objective measurement. OBJECTIVE: The purpose of this study was to evaluate the feasibility and clinical use of bedside sonographic assessment of gastric emptying by measuring the time to complete emptying of a standard volume of ingested water in patients after colorectal surgery. DESIGN: This was a prospective cohort study. SETTINGS: The study was conducted at a single tertiary institution in Sydney. PATIENTS: Healthy volunteers (n = 30) were studied to establish a reference range. Gastric emptying was then measured in patients (n = 39) before and after colorectal surgery. INTERVENTION: Assessment of gastric emptying was performed on days 1 to 4 by measuring antral cross-sectional area every 10 minutes after ingestion of 250 mL of water. MAIN OUTCOME MEASURES: The time to complete emptying of water was used as a surrogate measure of gastric emptying. Information concerning postoperative outcomes, GI symptoms, and recovery was also recorded. RESULTS: The median time to complete emptying of water for healthy volunteers was 20 minutes (range, 10-40 minutes). The study protocol was completed in 30 of 39 patients. The time to complete emptying of water on day 2 had the best discriminatory power to identify patients with ileus (sensitivity, 85.71%; specificity, 82.61%). Gastric emptying was normal in 20 of 30 (67%) patients, with only 1 case of ileus (false negative). These patients had less nausea (p = 0.0003), earlier intake of solid diet (p = 0.001), and shorter hospital stay (p = 0.040) compared with patients with abnormal gastric emptying. LIMITATIONS: Ultrasound is operator dependent with a learning curve. CONCLUSIONS: Bedside sonographic assessment of gastric emptying is feasible and reliable. Assessment of antral contents with a single ultrasound 40 minutes after ingestion of water enables classification of patients into those with normal and abnormal gastric emptying. When performed on postoperative day 2, it has good sensitivity/specificity for discriminating patients with ileus.

Association Rules Analysis of Comorbidity and Multimorbidity: The Concord Health and Aging in Men Project.

BACKGROUND: Comorbidity and multimorbidity are common in older people. Here we used a novel analytic approach called Association Rules together with network analysis to evaluate multimorbidity (two or more disorders) and comorbidity in old age. METHODS: A population-based cross-sectional study was undertaken where 17 morbidities were analyzed using network analysis, cluster analysis, and Association Rules methodology. A comorbidity interestingness score was developed to quantify the richness and variability of comorbidities associated with an index condition. The participants were community-dwelling men aged 70 years or older from the Concord Health and Ageing in Men Project, Sydney, Australia, with complete data (n = 1,464). RESULTS: The vast majority (75%) of participants had multimorbidity. Several morbidity clusters were apparent (vascular cluster, metabolic cluster, neurodegenerative cluster, mental health and other cluster, and a musculoskeletal and other cluster). Association Rules revealed unexpected comorbidities with high lift and confidence linked to index diseases. Anxiety and heart failure had the highest comorbidity interestingness scores while obesity, hearing impairment, and arthritis had the lowest (zero) scores. We also performed Association Rules analysis for the geriatric syndromes of frailty and falls to determine their association with multimorbidity. Frailty had a very complex and rich set of frequent and interesting comorbidities, while there were no frequent and interesting sets associated with falls. CONCLUSIONS: Old age is characterized by a complex pattern of multimorbidity and comorbidity. Single disease definitions do not account for the prevalence and complexity of multimorbidity in older people and a new lexicon may be needed to underpin research and health care interventions for older people.

Low levels of 25-hydroxy vitamin D and active 1,25-dihydroxyvitamin D independently associated with type 2 diabetes mellitus in older Australian men: the Concord Health and Ageing in Men Project.

OBJECTIVES: To examine the associations between serum 25-hydroxyvitamin D (25OHD) levels and the active vitamin D metabolite, 1,25-hydroxyvitamin D (1,25OHD), with type 2 diabetes mellitus (DM) in community-living men aged 70 and older. DESIGN: Cross-sectional. SETTING: A population-based, cross-sectional analysis of the baseline phase of the Concord Health and Ageing in Men Project (CHAMP), a large epidemiological study conducted in Sydney between January 2005 and May 2007. PARTICIPANTS: Community dwelling men aged 70 and older taking part in CHAMP (N = 1,659). MEASUREMENTS: Serum 25OHD and 1,25OHD levels, presence of DM, age, country of birth, season of blood collection, sun exposure, body mass index, vitamin D supplement use, statin use, income, measures of health, depression, activity of daily living disabilities, parathyroid hormone, estimated glomerular filtration rate, phosphate, and calcium. RESULTS: The prevalence of DM was 20.0%. There was a significant association between low 25OHD and 1,25OHD levels and DM that remained after adjustment for a wide range of confounders and covariates of clinical significance such as comorbidity, renal function, calciotropic hormones, and medications. CONCLUSION: 25OHD and 1,25OHD levels were associated with DM. The independent association between serum 25OHD and 1,25OHD concentrations and DM raises the question of whether each of the two vitamin D metabolites may influence DM through different biological mechanisms and pathways.

U-shaped association between serum 25-hydroxyvitamin D and fracture risk in older men: results from the prospective population-based CHAMP study.

The aim of this population-based, prospective, observational study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25OHD) and fracture risk in a cohort of 1662 community-dwelling men aged 70 to 97 years followed for a mean of 4.3 years. Data about mobility, muscle strength, balance, medication use, cognition, medical history, lifestyle factors, renal function, and serum 25OHD were collected at baseline. Data on radiologically verified fractures were collected every 4 months. The relationship between fractures and serum 25OHD levels was analyzed using Cox's proportional hazard regression. We accounted for bone mineral density, falls, physical activity, sun exposure, and season of blood draw, in addition to anthropometric and lifestyle factors, medical history, muscle strength, balance, and medication and supplement use. There were 123 first-incident fragility fractures. The relationship between baseline 25OHD and fracture risk was U-shaped, with increased fracture risk in men with either low or high serum 25OHD levels. In multivariate analysis, the risk of fracture was greatest in men with 25OHD levels in the lowest quintile (25OHD ≤36 nmol/L; hazard ratio [HR] = 3.5; 95% confidence interval [CI] 1.7-7.0) and in men in the highest quintile (25OHD >72 nmol/L; HR = 2.7; 95% CI 1.4-5.4) compared with men in the 4th quintile (25OHD ≥60 to ≤72 nmol/L). These associations were not explained by lower BMD, increased physical activity, fall risk, or other lifestyle or anthropomorphic factors. In community-dwelling older men, there appears to be a healthy target range for serum 25OHD concentrations. Thus, serum 25OHD levels too high and too low may be harmful in regard to fracture risk.

The relationship between solar UV exposure, serum vitamin D levels and serum prostate-specific antigen levels, in men from New South Wales, Australia: the CHAMP study.

PURPOSE: We aim to determine the relationship between season, personal solar UV exposure, serum 25(OH)D and 1,25(OH)2D and serum prostate-specific antigen (PSA) levels. METHODS: Questionnaire data and blood samples were collected at baseline from participants of the Concord Health and Ageing in Men Project (n = 1,705), aged 70 and above. They were grouped as men 'free of prostate disease' for those with no record of having prostate cancer, benign prostatic hyperplasia, or prostatitis and with serum PSA levels below 20 ng/mL, and 'with prostate disease' for those with a record of either of these diseases or with serum PSA levels 20 ng/mL or above. Personal solar UV exposure (sUV) was estimated from recalled hours of outdoor exposure and weighted against ambient solar UV radiation. Sera were analysed to determine levels of PSA, 25(OH)D and 1,25(OH)2D, and analysed using multiple regression, adjusting for age, BMI and region of birth. RESULTS: The association between sUV and serum PSA levels was conditional upon season (p interaction = 0.04). There was no direct association between serum PSA and 25(OH)D in both groups of men. There was a positive association between serum PSA and 1,25(OH)2D in men with prostate disease (mean = 110.6 pmol/L; p heterogeneity = 0.03), but there was no such association in men free of prostate disease (mean = 109.3 pmol/L; p heterogeneity = 0.8). CONCLUSION: The association between PSA and sUV may only be evident at low solar UV irradiance, and this effect may be independent of serum vitamin D levels.

The role of fat and lean mass in bone loss in older men: findings from the CHAMP study.

PURPOSE: Weight loss is associated with bone loss; however, it is unclear whether loss of fat or loss of lean body mass plays the key role in this relationship. The aim of this longitudinal analysis was to clarify the relationship between hip BMD, hip BMC and whole body BMC with changes in fat and lean tissue mass in older men. METHODS: The Concord Health and Aging in Men Project (CHAMP) is a population-based study in Sydney, Australia, involving 1705 men aged 70-97 years. Bone mineral density (BMD) of the total hip, and bone mineral content (BMC) of the hip and whole body (WB), lean mass and fat mass were measured with Dual X-ray Absorptiometry (DXA). Multivariate linear regression models were used to assess relationships. RESULTS: Over 2.2 years of follow-up, 368(33%) men lost at least 2% of their body weight, which included a mean loss of 0.8 kg/year of lean body mass and 0.9 kg/year of fat body mass. Fat loss was strongly associated with BMD loss in men who lost weight. As a group, weight losers lost 1.0% of hip BMD annually compared to 0.2% in men who gained weight, with each kilo of fat loss associated with 0.6%/year hip BMD loss (p<0.0001). Lean mass was not associated with hip BMD loss in weight losers, however, lean mass change was associated with BMD change in men who gained weight (0.3% hip BMD increase per kilo increase of lean mass p<0.01). CONCLUSION: Maintaining body weight is important for bone health in elderly men. Body fat plays an important role in this relationship, which may reflect the additional metabolic function of adipose tissue.